1. Field of the Invention
The present invention relates to a mixing method, a mixing device and a mixing system for mixing a small amount of liquid and a small amount of another liquid in a microfluidic system or the like.
2. Description of the Related Art
In recent years, a μ-TAS (Micro Total Analysis System) has drawn attention that uses a micromachining technique to microfabricate equipment for a chemical analysis or a chemical synthesis and then to perform the chemical analysis or the chemical synthesis in a microscale method. Compared to the conventional systems, a miniaturized μ-TAS has advantages in that required sample volume is small, reaction time is short, the amount of waste is small and others. The use of the μ-TAS in the medical field lessens the burden of patients by reducing volume of specimen such as blood, and lowers the cost of examination by reducing reagent volume. Further, the reduction of the specimen and reagent volume causes reaction time to shorten substantially, ensuring that examination efficiency is enhanced. Moreover, since the μ-TAS is superior in portability, it is expected to apply to broad fields including the medical field and an environmental analysis.
The present applicants have made various studies focusing attention on effects of microscale that is one of features of the μ-TAS due to the small dimensions. Since in the field of microchannel, dimensions are extremely small, flow velocity is extremely low and the Reynolds number is 200 or less, laminar flow should be expected, instead of turbulent flow in conventional reactors. Microspace is advantageous to diffusion and mixing in an interface with which laminar flow comes into contact, due to a large interfacial area in the microspace. The time required for mixing depends on a cross-sectional area of an interface with which two liquids come into contact and a thickness of a liquid layer. More specifically, according to a diffusion theory, the time T required for mixing is proportional to W2/D where a thickness of a liquid layer (a channel width) is denoted by W and diffusivity is denoted by D. Accordingly, when two liquids are flowed in channels in the form of laminar flow, the smaller a channel width is, the faster mixing (diffusion) time is. Further, the diffusivity D is derived from the following equation.(D=κb×T)/(6×π×μ×r)where T, μ, r, and κb represent liquid temperature, viscosity, particle radius and Boltzmann constant, respectively.
In short, molecule transport, reactions and separation are smoothly performed only by voluntary action of molecules or particles in a microspace without the use of mechanical agitation.
Further, conventionally, there are proposed an apparatus in which channels are crossed with one another in three dimensions for improvement in mixing efficiency (JP Patent No. 3119877) and an apparatus in which diffusion in the channel width direction is basically used and channels join together to carry out mixing (National Publication of International Patent Application No. PCT/CA98/00481).
As described above, conventionally, a study relating to a type of diffusion in the channel width direction is published and, in such a study, channels having a width of approximately 100 μm are the mainstream. In some applications, however, a problem arises of requiring a lot of time in the case of mixing by voluntary diffusion using channels having a width of 100 μm or so. Such a problem arises, for example, when a particle diameter is large. Further, when a reaction starts at the moment of interflow of liquids, the reaction proceeds prior to sufficient mixing, so that results in line with expectations cannot be obtained. In the event that a distance is short between a mixing portion and a detection portion, it is necessary to complete mixing in an extremely short time. To this end, a method is conceivable of reducing a channel width in order to shorten mixing time. Such a method, however, causes channel resistance to increase, leading to the difficulty in control of liquid transport.
Accordingly, the present applicants previously proposed a method for greatly reducing mixing time by forming extremely thin laminar streams along the flow direction of channels (Japanese unexamined patent publication No. 2003-220322).
According to the method previously proposed by the present applicants, when a mixing ratio is close to 1:1, mixing can be performed at a precise mixing ratio in a short time. When a mixing ratio is far from 1:1, however, it was found that uniform mixing is difficult at an intended mixing ratio due to influences of channel walls on a liquid having a smaller mixing ratio of two liquids as shown in FIG. 14.
Additionally, even if a ratio of amount of transported liquids is an intended value, there are some problems, including a problem that unevenness of concentration easily occurs in the channel width direction and a problem that it takes a lot of time to eliminate the unevenness of concentration by voluntary diffusion to provide uniform concentration.